Ten patients with severe systemic diseases, including systemic lupus erythematosus (n = 2), polymyositis (n = 2), essential mixed cryoglobulinaemia (n = 2), rheumatoid arthritis vasculitis (n = 3) and Wegener's granulomatosis (n = 1), were treated with 3 consecutive plasma exchanges synchronized with pulse cyclophosphamide. This therapeutic regimen was applied every 4 weeks initially and thereafter every 6 weeks in case of positive response after the first 3 cycles; it was combined in all patients with corticosteroid therapy. The treatment was administered for severe flare-up of the disease in 7 patients and for failure of previous treatments, including corticosteroids, cyclophosphamide and plasmapheresis, in 3 patients. Three kinds of response were observed: lasting complete remission without relapse after synchronization had ceased in 4 patients, partial clinical remission with post-synchronization relapse in 5 patients, and primary failure without any clinical response to treatment in only 1 patient. These results suggest that repeated plasma exchanges synchronized with cyclophosphamide are effective against progressive autoimmune diseases and in cases where conventionally administered immunosuppressive treatments had failed. However, this type of treatment cannot prevent long-term relapses, and only a prospective study can evaluate its success in terms of survival.